Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

ObjectiveTo investigate the association and translational mechanism between the hepatotoxicity of Xianling Gubao （XLGB） and its treatment of osteoporosis based on a zebrafish model. MethodsZebrafish were randomly selected four days after fertilization （4 dpf） and exposed to different concentrations of XLGB （0.7，0.35 mg·L^-1） for 96 h. At the endpoint of the exposure， the mortality rates of zebrafish in the treatment groups of different concentrations were counted， and the "dose-toxicity" curves were plotted. The 10% sublethal concentration （LC₁₀） was calculated. The liver area， acridine orange staining， and pathological tissue sections of transgenic zebrafish ［CZ16 （gz15Tg.Tg （fabp 10a： ds Red； ela31： EGFP）］ were used as indicators to confirm the hepatic damage caused by the sublethal concentration of XLGB. By using the prednisolone （PNSL）-induced osteoporosis model of zebrafish， the anti-osteoporosis activity of XLGB was evaluated by using the area of skull stained by alizarin red and the cumulative optical density value as indicators. Then， the toxicity difference of XLGB on the liver of zebrafish in healthy and osteoporotic states was compared， and the mechanism of the translational action of the toxicity of XLGB was predicted based on network pharmacology and real-time polymerase chain reaction（Real-time PCR）. ResultsThe LC₁₀ of XLGB on zebrafish （8 dpf） was 0.7 mg·L^-1. Compared with the blank group， the sublethal concentration （LC₁₀=0.7 mg·L^-1， 1/2 LC₁₀=0.35 mg·L^-1） of XLGB induced an increase in the number of apoptosis of hepatocytes in a dose-dependent manner， and the tissue arrangement of the liver was disordered and loose. The vacuoles were obvious， and the fluorescence area of the liver was significantly reduced （P<0.01）. Compared with the blank group， the mineralized area and cumulative optical density value of zebrafish skull in the PNSL model group were significantly reduced （P<0.01）， and those in the 0.7，0.35 mg·L^-1 XLGB treatment group were significantly increased compared with the model group （P<0.01）. Most importantly， 0.7 mg·L^-1 XLGB had no significant effect on the liver of zebrafish in the osteoporosis disease model compared with the blank group. The results of network pharmacology and real-time PCR experiments showed that the toxic transformation of XLGB might be related to the differences in the expression levels of key targets， such as tumor protein 53 （TP53）， cysteine aspartic acid specific protease-3（Caspase-3）， interleukin（IL）-6， and alkaline phosphatase（ALP） in different organismal states. ConclusionUnder certain conditions， XLGB has hepatotoxicity in normal zebrafish， but under osteoporotic conditions， XLGB not only exerts significant anti-osteoporosis activity but also alleviates hepatotoxicity significantly， which provides a reference for the safe clinical use of XLGB and real evidence for the theories of traditional Chinese medicine of attacking poison with poison and of treating disease with corresponding drugs without damage to the body.

Objective: To explore the plasma metabonomic characteristics of patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome. Methods: One hundred and three patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome were enrolled from November 2023 to February 2024 in the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and 54 healthy individuals were recruited. The general data of the two groups were analyzed, and the plasma metabolite content was detected using ultra-high performance liquid chromatography-Orbitrap mass spectrometry. Construct an orthogonal partial least squares discriminant analysis model to screen metabolites with significant intergroup changes. The variable importance in projection≥ 1, |log2FC|>1, and P<0.05 were used as the criteria for the screening of differential metabolites. Annotate differential metabolites using internal databases and the human metabolome database, and perform pathway analysis using MetaboAnalyst website. Results: There was no statistically significant difference in gender and age between the two groups.Seventeen potential differential metabolites were identified. The D-4′-phosphopantothenate, 2, 6-dichloroindophenol, 4-methylphenol, hypoxanthine, 11, 12-epoxyeicosatrienoic acids, oleamide, 3-phenyllactic acid contents were higher in patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome than in healthy individuals(P<0.05); 3-anisic acid, 3-iodo-octadecanoic acid, mebendazole, β-alanine, citric acid, trans-aconitic acid, geranyl diphosphate, lysophosphatidylcholine(18∶2), phosphatidylethanolamine(18∶1), and caprolactam contents were lower in patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome than in healthy individuals(P<0.05). Ten metabolic pathways were identified, including the key metabolic pantothenate and coenzyme A biosynthesis pathways. Conclusion Metabolic differences were observed between patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome and healthy individuals, and the underlying mechanism may involve the pantothenate and coenzyme A biosynthesis pathways, jointly mediated by D-4′-phosphopantothenate and β-alanine.

AIM: To evaluate the repeatability and accuracy of iCare IC100 tonometer in measuring intraocular pressure(IOP)by comparing the correlation and difference with Goldmann applanation tonometry(GAT)and non-contact tonometer(NCT), and to compare the correlation of the three types of IOP measurement with the central corneal thickness(CCT).METHODS: Prospective study. A total of 90 outpatients(90 eyes)in Liaoning Aier Eye Hospital from March 2019 to May 2019 were randomly selected as study subjects. All patients were measured IOP using iCare IC100, NCT, and GAT. The interclass correlation coefficient(ICC)was used to evaluate the repeatability of IOP measured 3 times consecutively using an intraocular tonometer. The correlation and consistency of iCare IC100, GAT and NCT were compared by one-way ANOVA, Pearson linear correlation analysis and Bland-Altman analysis. The linear regression analysis was used to analyze the correlation of the three tonometers with CCT.RESULTS: The mean IOP measured with iCare IC100, GAT and NCT was 19.74±6.90, 19.88±7.07 and 18.47±6.31 mmHg, respectively(F=1.180, P=0.309). The measurements of iCare IC100 with GAT, iCare IC100 with NCT and GAT with NCT were all positively correlated(r=0.930, 0.946, 0.918, all P<0.05), the Bland-Altman analysis showed that the mean differences between iCare IC100 and GAT, iCare IC100 and NCT, GAT and NCT were -0.142±2.61, 1.27±2.24, and 1.41±2.81 mmHg, respectively, with 97%(87/90), 96%(86/90), and 97%(87/90)IOP differences distributed within their 95% confidence intervals. The IOP measured with iCare IC100 and CCT, GAT and CCT and NCT and CCT were all positively correlated(r=0.426, 0.353, 0.451, all P<0.01). The linear regression equations between iCare IC100, GAT and NCT measurement and CCT were iCare IC100 IOP=-19.62+0.074×CCT; GAT IOP=-13.54+0.063×CCT; NCT IOP=-19.65+0.072×CCT; that is, for every 10 μm increase in CCT, iCare IC100 measurement increased by 0.74 mmHg, GAT measurement increased by 0.63 mmHg, and NCT measurement increased by 0.72 mmHg.CONCLUSION: The iCare IC100 tonometer has good repeatability and accuracy in measuring IOP, and the CCT has a greater impact on the measurement of iCare IC100 than the GAT and NCT.

AIM: To evaluate the repeatability and accuracy of iCare IC100 tonometer in measuring intraocular pressure(IOP)by comparing the correlation and difference with Goldmann applanation tonometry(GAT)and non-contact tonometer(NCT), and to compare the correlation of the three types of IOP measurement with the central corneal thickness(CCT).METHODS: Prospective study. A total of 90 outpatients(90 eyes)in Liaoning Aier Eye Hospital from March 2019 to May 2019 were randomly selected as study subjects. All patients were measured IOP using iCare IC100, NCT, and GAT. The interclass correlation coefficient(ICC)was used to evaluate the repeatability of IOP measured 3 times consecutively using an intraocular tonometer. The correlation and consistency of iCare IC100, GAT and NCT were compared by one-way ANOVA, Pearson linear correlation analysis and Bland-Altman analysis. The linear regression analysis was used to analyze the correlation of the three tonometers with CCT.RESULTS: The mean IOP measured with iCare IC100, GAT and NCT was 19.74±6.90, 19.88±7.07 and 18.47±6.31 mmHg, respectively(F=1.180, P=0.309). The measurements of iCare IC100 with GAT, iCare IC100 with NCT and GAT with NCT were all positively correlated(r=0.930, 0.946, 0.918, all P<0.05), the Bland-Altman analysis showed that the mean differences between iCare IC100 and GAT, iCare IC100 and NCT, GAT and NCT were -0.142±2.61, 1.27±2.24, and 1.41±2.81 mmHg, respectively, with 97%(87/90), 96%(86/90), and 97%(87/90)IOP differences distributed within their 95% confidence intervals. The IOP measured with iCare IC100 and CCT, GAT and CCT and NCT and CCT were all positively correlated(r=0.426, 0.353, 0.451, all P<0.01). The linear regression equations between iCare IC100, GAT and NCT measurement and CCT were iCare IC100 IOP=-19.62+0.074×CCT; GAT IOP=-13.54+0.063×CCT; NCT IOP=-19.65+0.072×CCT; that is, for every 10 μm increase in CCT, iCare IC100 measurement increased by 0.74 mmHg, GAT measurement increased by 0.63 mmHg, and NCT measurement increased by 0.72 mmHg.CONCLUSION: The iCare IC100 tonometer has good repeatability and accuracy in measuring IOP, and the CCT has a greater impact on the measurement of iCare IC100 than the GAT and NCT.

Objective: To examine the impacts of chemotherapy/radiotherapy, targeted therapy, and combined treatment on the quality of life in patients with intermediate and advanced lung cancer. Methods: The patients with intermediate and advanced lung cancer undergoing chemotherapy/radiotherapy, targeted therapy, and combined treatment for the first time were recruited from a tertiary hospital in Weifang City, Shandong Province, using a quota sampling method in September 2023. Basic information was collected using a general information questionnaire, and the quality of life was assessed using the Chinese version of Functional Assessment of Cancer Therapy-General. The investigation started on the 7th day of treatment, and the follow-ups were conducted at 3 and 6 months. The quality of life in patients with different treatment regimens and at different treatment time were compared using repeated measure analysis of variance. Results: There were 26 chemotherapy/radiotherapy patients, 32 targeted therapy patients, and 95 combination therapy patients. There were no significant differences in age, gender, place of residence, education level, self-rated economic status, medical insurance, pathological type and disease stage among the three treatment regimens (all P>0.05). The repeated measure analysis of variance showed an interaction effect between time and group among patients receiving the three treatment regimens (P<0.05). The quality of life scores of patients receiving combination therapy decreased with extended treatment time (all P<0.05). The quality of life scores of patients receiving targeted therapy at 3 and 6 months were lower than those treated for 7 days (both P<0.05). No significant differences were observed in quality of life scores among chemotherapy/radiotherapy patients with different treatment durations (all P>0.05). At 3 and 6 months, patients receiving combination therapy had lower quality of life scores compared to those receiving chemotherapy/radiotherapy or targeted therapy (all P<0.05). Conclusion The decline in quality of life for patients with intermediate and advanced lung cancer undergoing chemotherapy/radiotherapy and targeted therapy is less than that for patients receiving combined therapy.

ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats （SHR）. In this experiment， 50 SHR rats were randomly grouped as follows： model （n=8）， captopril （0.01 g·kg^-1） （n=6）， low-dose blank Fufang Lingjiao Jiangya pills （0.342 g·kg^-1） （n=6）， high-dose blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1） （n=6）， low-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， high-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）， low-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， and high-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）. Additionally， 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration， 3 h post administration， and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions， 48 SHR rats were randomly grouped as follows： model， blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1）， antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1）， 2× goat horn-containing Fufang Lingjiao Jiangya pills （0.824 g·kg^-1）， 4× goat horn Fufang Lingjiao Jiangya pills （0.969 g·kg^-1）， and 6× goat horn Fufang Lingjiao Jiangya pills （1.112 g·kg^-1）. The normal group included 8 WKY rats， and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks， and blood pressure was recorded at various time points （pre-administration， 3 h post administration， and on days 4， 7， 10， and 14 of administration）. Serum levels of angiotensin-converting enzyme （ACE）， angiotensin Ⅱ（Ang Ⅱ）， renin， and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart， kidney， and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2， angiotensin Ⅱ type 1 receptor （AT1R）， and angiotensinogen （AGT） in the kidney tissue were determined by Western blot， while the expression of nuclear factor （NF）-κB p65 and Toll-like receptor 4 （TLR4） in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group， all treatment groups showed lowered blood pressure （P<0.05， P<0.01）， and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group， the model group showed elevated serum levels of ACE， Ang Ⅱ， renin， and IL-6， while the elevations were declined in the Fufang Lingjiao Jiangya pills groups （P<0.05， P<0.01）. Pathological changes in the heart， kidney， and thoracic aorta were alleviated in all the treatment groups， with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R， AGT， NF-κB p65， and TLR4 and up-regulated protein levels of ACE2 （P<0.05， P<0.01） compared with model group， with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system （RAAS） and TLR4/NF-κB signaling pathways.

Background Work-related musculoskeletal disorders (WMSDs), as one of the major occupational health issues worldwide, have shown an increasing positive rate year by year. Due to the unique demands of work, operating room nurses exhibit a higher positive rate of WMSDs compared to other occupational groups, necessitating active attention and intervention. Objective To estimate the prevalence of WMSDs among operating room nurses in tertiary hospitals, explore the characteristics and latent categories of WMSDs, and analyze the influencing factors associated with the occurrence of WMSDs. Method Using a randomized cluster sampling method, operating room nurses from nine tertiary hospitals in Urumqi were selected as study participants between December 2023 and January 2024. Data were collected through a general information questionnaire, an ergonomic questionnaire for operating room nurses, and the Chinese Musculoskeletal Disorders Questionnaire. Latent class analysis was employed to examine the patterns of WMSDs among the nurses, while chi-square test and multinomial logistic regression were utilized to analyze the influencing factors of WMSDs. Result A total of 411 valid questionnaires were collected in this survey. The positive rate of WMSDs among operating room nurses in the tertiary hospitals of Urumqi over the past year was 91.9%. The positive rates, ordered from highest to lowest by body region, were neck (79.1%), shoulders (70.3%), and lower back (68.1%). The operating room nurses were categorized into three distinct groups by latent class analysis: multi-site pain group, neck-shoulder-back pain group, and neck and lower back pain group. The results of the multinomial logistic regression models revealed that gender, job strain level, ergonomic load level in the operating room, and exposure to cold or drafty working conditions or not were significant influencing factors for reporting WMSDs among operating room nurses. Specifically, having less than 5 years of work experience, low ergonomic load level, low job strain, and moderate job strain were identified as protective factors against WMSDs. Conversely, exposure to cold or drafty working environments and being female were identified as risk factors for WMSDs. The logistic regression models also indicated that compared to the neck-lower back pain group, the neck-shoulder-back pain group had a higher probability of reporting low job strain (OR=0.168, 95%CI: 0.029, 0.968) and being female (OR=4.847, 95%CI: 2.506, 9.378). In contrast, when comparing to the neck-lower back pain group, the multi-site pain group had a higher probability of reporting, low-level ergonomic workload (OR=0.079, 95%CI: 0.015, 0.412), low job strain (OR=0.019, 95%CI: 0.002, 0.145), moderate job strain (OR=0.080, 95%CI: 0.016, 0.401), high job strain (OR=0.132, 95%CI: 0.027, 0.647), less than 5 years of work experience (OR=0.173, 95%CI: 0.044, 0.683), being female (OR=2.424, 95%CI: 1.130, 5.200), and exposure to cold or drafty working environments (OR=3.277, 95%CI: 1.657, 6.481). Conclusion The positive rate WMSDs among operating room nurses in tertiary hospitals is notably high in Urumqi, with distinct co-occurrence characteristics observed within the population. To mitigate the risk of WMSDs, it is essential to implement targeted health education and prevention training programs tailored to different patterns of WMSDs. Additionally, improving working conditions, optimizing human resource allocation , and other proactive measures should be undertaken. These efforts will effectively reduce the incidence of WMSDs among operating room nurses and safeguard their occupational health.

ObjectiveGliomas in the motor functional area can damage the corticospinal tract (CST), leading to motor dysfunction. Currently, there is a lack of unified methods for evaluating the extent of CST damage, especially in patients with high surgical risk where the minimum distance from the lesion to the CST is less than 10 mm. This study aims to further clarify the classification method and clinical significance of CST morphological changes in these patients. MethodsThis retrospective study analyzed 109 high-risk functional area glioma patients who underwent neurosurgical treatment with preoperative diffusion tensor imaging (DTI) imaging and intraoperative neurostimulation guidance between 2014 and 2024. All patients had a lesion-to-tract distance (LTD) of less than 10 mm between the CST and the lesion. Preoperative DTI evaluation of CST involvement-induced morphological changes were reviewed. Patients were divided into 3 groups: 17 cases (15.6%) with symmetric CST morphology compared to the healthy side (CST symmetry), 48 cases (44.0%) with significant CST morphology changes compared to the healthy side (CST deformation), and 44 cases (40.4%) with CST overlap with the tumor (CST overlap). Then we classified patients according to preoperative assessment of tumor-induced morphological changes, and analyze postoperative motor function for each category. ResultsPostoperative pathology showed a significantly higher proportion of high-grade gliomas (HGG) in the CST overlap group compared to the other two groups (P=0.001). Logistic regression analysis showed that CST overlap was a predictor of HGG (P=0.000). The rate of total tumor resection in the CST deformation group and overlap group was lower than in the CST symmetric group (P=0.008). There was a total of 41 postoperative hemiplegic patients, with 4 cases (23.5%) in the CST symmetric group, 11 cases (22.9%) in the CST deformation group, and 26 cases (59.1%) in the CST overlap group. CST overlap with the tumor predicted postoperative hemiplegia (P=0.016). Two-way ANOVA analysis of the affected/healthy side and CST morphology groups showed significant main effects of CST grouping and healthy-affected side (P=0.017 and P=0.010), with no significant interaction (P=0.31). The fractional anisotropy (FA) value in the CST overlap group and the affected side was lower. A decrease in the FA value on the affected side predicted postoperative hemiplegia (sensitivity 69.2%, specificity 71.9%). ConclusionWe have established a method to predict postoperative hemiplegia in high-risk motor functional area glioma patients based on preoperative CST morphological changes. CST overlap leads to a decrease in CST FA values. This method can be used for precise patient management and aid in accurate preoperative surgical planning.